Computational Model and Dynamics of Monomeric Full-Length APOBEC3G

Area of Science:

• Structural Biology
• Virology
• Biophysics

Background:

• APOBEC3G (A3G) is a key innate immunity protein restricting HIV-1 replication in the absence of viral infectivity factor (Vif).
• Understanding A3G's structure is crucial for elucidating its interaction mechanisms and antiviral functions.

Purpose of the Study:

• To determine the structural dynamics of full-length APOBEC3G (A3G).
• To validate computational models of A3G using experimental techniques.

Main Methods:

• Computational modeling including docking and molecular dynamics simulations.
• Time-lapse high-speed atomic force microscopy (HS-AFM) of hydrated A3G.

Main Results:

• A computer model of A3G revealed large-scale dynamics, with domains capable of compact or extended dumbbell conformations.
• HS-AFM confirmed A3G exists in globular (~84%) and dumbbell (~16%) forms, dynamically interconverting.
• Simulations accurately captured A3G's transition from DNA-bound to closed states.

Conclusions:

• Monomeric A3G possesses a dynamic nature, switching between distinct structural forms.
• This dynamic behavior is essential for A3G's target recognition, including DNA scanning and interaction with viral RNA.
• The findings provide insights into A3G's antiviral mechanisms against HIV-1.